The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

Aim: We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Method: Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. Results: A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. Conclusion: High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Cardiometabolic-related dietary patterns and thyroid function: a population-based cross-sectional study.

BACKGROUND: Little is known about the association of dietary patterns with thyroid function. Since thyroid function and cardiometabolic variables are inter-related, we investigated whether cardiometabolic-related dietary patterns are associated with thyroid function. METHODS: This cross-sectional study included 3520 Tehran Lipid and Glucose Study participants. Reduced rank regression was used to find dietary patterns with body mass index, serum fasting glucose, triglycerides, HDL-C, and systolic and diastolic blood pressures as response variables. Two patterns were retained, one based on 35 food groups (native-based pattern) and the other based on the European Prospective Investigation into Cancer and Nutrition Germany (EPIC) food grouping (n = 33). A confirmatory cardio-metabolic dietary pattern was also created according to the weight of food groups proposed by the Framingham Offspring Study (FOS). The association of each pattern with thyroid-stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibody (TPOAb) and the odds of thyroid dysfunction was examined by linear and logistic regression, respectively. RESULTS: The two exploratory dietary patterns were highly correlated and associated with greater TSH levels in euthyroid participants. The adjusted odds ratio (95% CI) of subclinical hypothyroidism per one standard deviation was 1.14 (1.01, 1.28) for the native-based pattern and 1.16 (1.03, 1.31) for the EPIC-based pattern. The odds of subclinical hypothyroidism was significantly greater in the second and third tertiles of the native-based pattern compared to the first tertile in the adjusted model (p-trend = 0.005). The odds of subclinical hypothyroidism increased across the tertiles of the EPIC-based pattern, but the odds was significantly higher only in tertile 3 compared to tertile 1, with an OR (95% CI) of 1.44 (1.07, 1.94) in the adjusted model. The adjusted odds of clinical hypothyroidism were greater in tertile 3 of the native-based pattern compared with tertile 1 (OR = 1.65, 95% CI 1.04, 2.62). The patterns were unrelated to hyperthyroidism or TPOAb positivity. The FOS-based confirmatory score was unrelated to thyroid function. CONCLUSIONS: A diet high in fast foods, soft drinks, and legumes and low in confectionery, potatoes, butter, and jam and honey was associated with higher TSH levels in euthyroidism and higher odds of subclinical hypothyroidism.

Association of trajectory of body shape index with all-cause and cause-specific mortality: 18 years follow-up.

Objectives: The current study aimed to examine how the trajectory of a body shape index (ABSI) could predict mortality in a prospective cohort of 5587 participants. Methods: A Growth Mixture Model (GMM) was employed to identify ABSI and body shape trajectories spanning from 2000 to 2018. Multivariate Cox regression models with hazard ratio (HR) and 95% confidence intervals (CIs) were built to assess the association of death from all-cause and cardiovascular disease (CVD) with ABSI and body shape trajectories. Results: We found that individuals with a low ABSI-marked increase (Class II) and high ABSI-marked increase trajectory (Class III) had a higher risk of all-cause (adjusted HR for Class II, 1.37; 95%CI, 1.04-1.79; adjusted HR for Class III, 1.42; 95%CI, 1.05-1.91) and non- CVD mortality (adjusted HR for Class II, 1.38; 95%CI, 1.00-1.91; adjusted HR for Class III, 1.42; 95%CI, 1.00-2.05) as well as an increased risk of CVD (adjusted HR for Class II, 1.40; 95%CI, 1.14-1.71; adjusted HR for Class III, 1.42; 95%CI, 1.13-1.78) and coronary heart disease (CHD) (adjusted HR for Class II, 1.52; 95%CI, 1.18-1.96; adjusted HR for Class III, 1.47; 95%CI, 1.11-1.95. The trajectories of body shape phenotypes did not show any significant associations with mortality, CVD, or CHD events. Conclusions: ABSI trajectories might be associated with subsequent risk of mortality and CVD events.

The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis.

Type 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges's g:1.55, 95%CI 0.93-2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges's g: - 0.30, 95%CI - 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.

Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes.

BACKGROUND: The available evidence indicates that the severity of metabolic syndrome tends to worsen progressively over time. We assessed the trajectory of age and sex-specific continuous MetS severity score (cMetS-S) and its association with the development of diabetes during an 18-year follow-up. METHODS: In a prospective population-based Tehran Lipid and Glucose Study, 3931 eligible participants free of diabetes, aged 20-60 years, were followed at three-year intervals. We examined the trajectories of cMetS-S over nine years using latent growth mixture modeling (LGMM) and subsequent risks of incident diabetes eight years later. The prospective association of identified trajectories with diabetes was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥ 30 kg/m2), antihypertensive and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner. RESULTS: Among 3931 participants, three cMetS-S trajectory groups of low (24.1%), medium (46.8%), and high (29.1%) were identified during the exposure period. Participants in the medium and high cMetS-S trajectory classes had HRs of 2.44 (95% CI: 1.56-3.81) and 6.81 (95% CI: 4.07-10.01) for future diabetes in fully adjusted models, respectively. Normoglycemic individuals within the high cMetS-S class had an over seven-fold increased risk of diabetes (HR: 7.12; 95% CI: 6.05-12.52). CONCLUSION: Although most adults exhibit an unhealthy metabolic score, its severity usually remains stable throughout adulthood over ten years of follow-up. The severity score of metabolic syndrome has the potential to be utilized as a comprehensive and easily measurable indicator of cardiometabolic dysfunction. It can be employed in clinical settings to detect and track individuals at a heightened risk of developing T2DM, even if their glucose levels are normal.

Independent association between age- and sex-specific metabolic syndrome severity score and cardiovascular disease and mortality.

Traditional metabolic syndrome (MetS) criteria have several limitations, which hinder its use in clinical practice. To overcome the limitations, we investigated the association between age- and sex-specific continuous MetS severity score (cMetS-S) and cardiovascular disease (CVD) and mortality beyond MetS components in the framework of the Tehran Lipid and Glucose Study. Participants aged 20-60 years at baseline were included in the study. We excluded participants with CVD, cancer, use of corticosteroids, estimated glomerular filtration rate < 30 ml/min/1.73 m2, and those who were pregnant. We evaluated the association between cMetS-S with CVD and mortality over 18 years of follow-up among 8500 participants with continuous and quantile approaches using the Cox proportional hazard regression model. In addition, the model performance of cMetS-S for predicting CVD events was compared to the conventional MetS criteria. Participants with higher cMetS-S had a significantly increased risk for CVD, coronary (CHD) and non-coronary heart disease (non-CHD), and all-cause, cardiovascular, and sudden cardiac death. Independent of the confounders and MetS components, the cMetS-S had the HRs of 1.67 (95% CI 1.47-1.89), 1.60 (95% CI 1.37-1.86), and 1.88 (95% CI 1.50, 2.35) for CVD, CHD, and non-CHD events upon 1-SD increment, respectively. The risk of mortality was increased for 1-SD of cMetS-S (all-cause mortality, HR 1.24; 95% CI 1.09-1.41; CVD mortality, HR 1.72; 95% CI 1.20-2.45; sudden cardiac death, HR 1.60; 95% CI 1.03-2.49). The model fitness of cMetS-S was superior to the conventional MetS criteria in predicting CVD and mortality. The cMetS-S provided an additional risk for CVD and mortality beyond the individual MetS components. Standardized cMetS-S could be a potential universal measure to define MetS severity while considering the weighted contribution of MetS components and their variations by age, sex, and ethnicity.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial.

BACKGROUND: Understanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients. METHODS: Radioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 µg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 - 24 were calculated at the last visit. RESULTS: Serum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 - 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group. CONCLUSION: Combined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested. IRCT REGISTRATION NUMBER: IRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13 . Registration date: 08/12/2021.

Development and validation of a continuous metabolic syndrome severity score in the Tehran Lipid and Glucose Study.

Metabolic syndrome (MetS), defined as the coexistence of interrelated cardiometabolic risk factors, is limited by ignoring the severity of the disease and individuals with a pre-metabolic state. We aimed to develop the first age- and sex-specific continuous MetS severity score in the adult population using confirmatory factor analysis (CFA) based on the MetS components in the Middle East. Using data from the population-based Tehran Lipid and Glucose Study (TLGS) I and II datasets, we conducted CFA of the single factor MetS on 8933 adults (20-60 years old) totally, and in age and sex subgroups. We allowed for different factor loadings across the subgroups to formulate age- and sex-specific continuous MetS severity score equations. Thereafter, we validated these equations in the dataset of TLGS III participants. Triglyceride had the highest factor loading across age and sex subgroups, indicating the most correlation with MetS. Except for women aged 40-60 years, waist circumference was the second most significant factor contributing to MetS. Systolic blood pressure was more closely related to MetS in women than in men. Systolic blood pressure and fasting plasma glucose had the weakest correlation with MetS among the 40-60 age group. Moreover, as women age, the contribution of fasting plasma glucose to MetS tended to decline, while it remained relatively constant in men. The resulting MetS severity score was correlated with age and homeostasis model assessment of insulin resistance. Furthermore, the continuous MetS severity score well predicted the traditional MetS according to receiver operating characteristic analysis in the validation dataset. The age- and sex-specific continuous MetS severity score for the West Asian adult population provides a tangible quantitative measure of MetS enabling clinicians to screen and monitor the individuals at risk and assess their metabolic trends.

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine.

OBJECTIVE: The aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism. METHODS: A total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment. RESULTS: The rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up. CONCLUSION: Progression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.

The impact of metabolic syndrome on chronic kidney disease development. Insights from a big prospective study.

BACKGROUND: Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed the association between metabolic syndrome (MetS) and CKD. Current evidence is from cross-sectional studies. There is a need for the robust data from big prospective cohort studies with long-term follow-up. This study investigated the association between CKD and MetS after 18 years of follow-up. MATERIAL AND METHOD: Among 15,255 participants aged ≥20 years at baseline (1999-2005), after exclusion of CKD, cancer, and use of corticosteroids, 8987 participants entered the study and followed at a three-year cycle up to 2018. All participants were divided into five subgroups: (1) MetS-free, (2) MetS (DM+, HTN-), (3) MetS+ (DM-, HTN+), (4) MetS+ (DM+, HTN+) and (5) MetS+ (DM-, HTN-). RESULT: At baseline, the mean age of the participants was 39.8 ± 13.3 years; 4996 (55.6%) were females. CKD was developed in 2038 (22.7%) subjects during 18 years of follow-up, of whom 1107 had MetS. After adjusting for the confounding variables, MetS (DM+, HTN+) subgroup had the highest risk of CKD (HR = 1.51, 95% CI = 1.32-1.71). MetS subjects with five components had a higher incidence rate of CKD (HR = 1.43, 95% CI = 1.22-1.68). There was no association between high waist circumference (WC) (HR = 1.08, 95% CI = 0.99-1.19) and high-density lipoprotein (HDL) (HR = 1.07, 95% CI = 0.98-1.18) with CKD. CONCLUSION: CKD significantly develops in patients with MetS. Metabolic syndrome was associated with the development of chronic kidney disease incidence. Hypertension, diabetes, and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD.

Sex-specific Trajectories of Insulin Resistance Markers and Reduced Renal Function During 18 Years of Follow-up: TLGS.

CONTEXT: The evidence suggest that insulin resistance (IR) complicates chronic kidney disease (CKD); however, the longitudinal association of IR with development of CKD is unknown. OBJECTIVE: This work aimed to investigate the association between the dynamic course of insulin resistance and CKD. METHODS: In the longitudinal, population-based Tehran Lipid and Glucose Study, 3071 eligible participants aged 20 years or older were followed for 18 years at 3-year intervals. Homeostatic model assessment of insulin resistance (HOMA-IR) and clinical surrogate markers of IR, including triglyceride-glucose index (TyG), visceral adiposity index (VAI), and lipid accumulation product (LAP), were calculated. Using latent variable mixture modeling, sex-specific trajectories were plotted for each IR marker. Trajectory group association of the IR markers with CKD was determined using the multivariable Cox proportional-hazards regression model. RESULTS: For HOMA-IR, 2 distinct trajectory patterns (stable and increasing), and for TyG, VAI, and LAP, 3 trajectories (low, moderate, and high) were identified. The participants with an increasing HOMA-IR trajectory had a significantly increased risk of CKD in men (hazard ratio [HR]: 1.72; 95% CI, 1.06-2.79) and women (HR: 1.37; 95% CI, 1.00-1.89) after adjusting for confounding variables. The high TyG and VAI trajectory classes were associated with a higher risk of CKD than the low TyG and VAI trajectory classes both in men (TyG: HR: 1.97; 95% CI, 1.12-3.46; VAI: HR:1.66; 95% CI, 1.06-2.62) and women (TyG: HR: 1.50; 95% CI, 1.06-2.12; VAI: HR:1.66; 95% CI, 1.20-2.31). In contrast, the high LAP (HR: 3.38; 95% CI, 2.08-5.48) trajectory was associated with incident CKD only in women. CONCLUSION: An increasing trend of HOMA-IR is associated with a higher risk of CKD in men and women. Among clinical IR surrogate markers, abnormal trajectory patterns of LAP in women and TyG and VAI in both sexes are associated with a higher risk of CKD.

BMI variability and incident diabetes mellitus, Tehran Lipid and Glucose Study (TLGS).

Previous epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20-60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals' BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94-1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10-1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01-1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08-1.19, p < 0.001) in women with BMI ≥ 25 kg/m2. In men with a baseline BMI ≥ 25 kg/m2, BMI-RMSE was associated with a decreased risk of T2DM (HR: 0.71, 95% CI: 0.53-0.93, p = 0.015). Baseline BMI was not associated with the risk of diabetes in men and women. Positive BMI slope is associated with the development of diabetes in both sexes. The association of BMI variability with incident T2DM differs according to sex and baseline BMI. BMI variability is associated with a lower risk of T2DM in overweight and obese men. BMI variability in women and baseline BMI in both gender are not related to the risk of T2DM.

Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter.

BACKGRUOUND: This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI). METHODS: In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter. RESULTS: After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group. CONCLUSION: In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments.

OBJECTIVE: The aim of this study was to compare the "time to euthyroidism" and "time spent in euthyroidism" following methimazole (MMI) and radioactive iodine (RAI) treatments. METHODS: Three hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared. RESULTS: The mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%. CONCLUSION: In our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.

Anthropometric measures and risk of all-cause and cardiovascular mortality: An 18 years follow-up.

BACKGROUND: The contribution of anthropometric measures to predict mortality in normal-weight subjects is unclear. We aimed to study the association of central obesity measures, e.g., waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), with the risk of all-cause and CVD mortality. METHODS: In a prospective population-based Tehran Lipid and Glucose Study, 8287 participants aged ≥30 y, followed for a median of 18 years. The association of WC, WHR and WHtR with the risk for mortality was estimated using multivariate Cox proportional hazard models in different BMI groups. RESULTS: We documented 821 deaths, of which 251 were related to CVD mortality. Normal weight individuals with central obesity were significantly at increased risk of all-cause (HR: 1.5; 95% CI: 1.10, 2.1) and CVD mortality (HR: 1.6; 95% CI: 0.92, 2.9) compared with normal-weight individuals without central obesity; the risk remained significant only in women. Also, normal-weight women (not men) with high WHR were at increased risk of all-cause (HR: 1.7; 95% CI: 1.0, 2.8) and CVD mortality (HR: 5.9; 95% CI: 1.5, 23.2). High WHtR increased the risk of all-cause (HR: 1.5; 95% CI: 1.2, 1.8) and CVD mortality (HR: 1.8; 95% CI: 1.2, 2.7) which remained significant in normal-weight men and women. All central obesity indicators were significantly associated with all-cause and CVD mortality in subjects aged under 65. CONCLUSION: Even in normal-weight individuals, WC and WHR in women and WHtR in both sexes are predictors of all-cause and CVD mortality. WHtR shows a stronger association, especially in the population aged under 65.

Reduced Sensitivity to Thyroid Hormone Is Associated with Diabetes and Hypertension.

CONTEXT: Recently, reduced sensitivity to thyroid hormone as a more common finding in the general population and its possible association with metabolic parameters has been the focus of attention. OBJECTIVE: The objective was to evaluate the cross-sectional association of thyroid hormone sensitivity with diabetes, metabolic syndrome (MetS), and its components. METHODS: The study included a Tehranian representative sample of 5124 subjects aged ≥20 years participating in the Tehran Thyroid Study (2008-2011). Body weight, waist circumference, and blood pressure (BP) were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose, insulin, free thyroxine (fT4), and thyrotropin (TSH) were assayed. Thyroid hormone resistance was calculated by the Thyroid Feedback Quantile-based Index (TFQI) and Iranian-referenced Parametric TFQI (PTFQI) and compared with 2 other indices: Thyrotroph T4 Resistance Index (TT4RI) and TSH Index. RESULTS: TFQI was significantly associated with high BP MetS criterion (OR = 1.14, 95% CI: 1.06, 1.23) and diabetes mellitus (OR = 1.16, 95% CI: 1.04, 1. 30, P = .009) in euthyroid subjects after adjusting for age, sex, smoking, physical activity, body mass index, and Homeostasis Model Assessment Index for Insulin Resistance. TFQI was not associated with new-onset diabetes contrary to known diabetes in subgroup analysis. The results were similar for PTFQI. TSHI (OR = 1.22, 95% CI: 1.08, 1.38, P = .001) and TT4RI (OR = 1.08, 95% CI: 1.01, 1.16, P < .001) were associated only with high BP in euthyroid subjects. CONCLUSION: The new TFQI index seems to be the indicator of reduced sensitivity to thyroid hormone most suitable to associate its population variations with diabetes and hypertension in euthyroid subjects; however, interpretation for diabetes should be concerned with cautions, necessitating future studies.

Incidence of Thyroid Dysfunction Facing Metabolic Syndrome: A Prospective Comparative Study with 9 Years of Follow-Up.

BACKGROUND: Studies assessing thyroid hormones in metabolic syndrome (MetS) patients are contradictory. Also, the effect of MetS on thyroid function over time is not yet evaluated. This study investigated the prevalence and incidence of thyroid dysfunction (TD) as well as time trends of thyroid hormones in subjects with and without MetS, during a 10-year follow-up in Tehranian adult population. METHODS: This is a prospective cohort study conducted in the framework of Tehran Thyroid Study on 5,786 subjects aged ≥20 years: 4,905 eligible participants entered the study after excluding those with corticosteroid or radioactive iodine use, pregnancy, thyrotropin (TSH) <0.1 and >10 mU/L, and missing data. Physical examinations were performed and serum concentrations of TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), fasting plasma glucose, insulin, and lipid profile were assessed at baseline and 3-year intervals during the follow-up. MetS was defined according to the Joint Interim Statement Definition. RESULTS: At baseline, there were no difference in median serum concentrations of FT4 and TSH between MetS and non-MetS group after adjusting for age, sex, BMI, smoking, and TPOAb positivity. Although there was higher risk of overt (42%) and subclinical hypothyroidism (16%) in MetS compared with non-MetS subjects, no significant difference was observed in adjusted ORs for any TD between 2 groups. There were also no significant differences in time trends of TSH, FT4, TPOAb positivity, and incidence rates of TDs between MetS and non-MetS groups during 10 years, after adjustment for age, sex, BMI, smoking status, and TPOAb positivity. CONCLUSION: MetS is not associated with thyroid hypofunction considering other important confounders such as age, sex, smoking, BMI, and TPOAb positivity. There is also no difference in the trend of thyroid hormones and incidence of TD between MetS and non-MetS subjects during a 10-year follow-up.

Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study.

BACKGROUND: Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals. METHOD: This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group. RESULTS: We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism's overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15-3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04-1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results. CONCLUSIONS: Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.

Iranian Endocrine Society Guidelines for Screening, Diagnosis, and Management of Gestational Diabetes Mellitus.

CONTEXT: Gestational diabetes mellitus (GDM) is an important endocrine disorder in perinatology, associated with several maternal and neonatal complications. Development of national guidelines can inform clinicians, health policymakers, and researchers about the most recent evidence and practical issues of diagnosis and management of GDM. OBJECTIVES: We aimed to develop clinical practice guidelines for the diagnosis and management of GDM in Iranian pregnant women. EVIDENCE ACQUISITION: The Iranian Endocrine Society constituted a task force, consisting of obstetrician-gynecologists, endocrinologists, a clinical nutritionist, a clinical epidemiologist, and a librarian, to review the published literature and propose national guidelines for the diagnosis and management of GDM. The consensus was reached on all recommendations in several group meetings with a majority decision. The evidence and recommendations were graded according to the American College of Physicians' Guideline Grading System. RESULTS: The proposed guidelines included recommendations for screening, diagnosis, and management of GDM in Iran. CONCLUSIONS: By using an evidence-based approach, these national GDM guidelines can address important clinical issues in the diagnosis and management of Iranian women with GDM.